Biomaterials Advances
·
2026
·
IF 6.7
Ling Peng,Yusong Pan,Jun Tao,Cuilian Wei,Qianqian Liu,Run Huang,Xiuling Lin,Rui Yue
To address core issues in spinal cord injury repair such as oxidative stress, excessive inflammation and impaired nerve regeneration, this study developed a 3D-printed multifunctional PCP-Res-NGF scaffold. The scaffold achieves stable loading of resveratrol and nerve growth factor by sequentially coating chitosan and polydopamine on the polylactic acid skeleton. Experiments show that the scaffold has pH/ROS dual-responsive drug release characteristics, fitting the S-type Weibull model in simulated injury environments and following a first-order kinetic model under physiological conditions; it exhibits significant scavenging capabilities against DPPH, ·OH, and H 2 O 2 , effectively reducing intracellular ROS levels, an effect attributed to the radical quenching properties of polydopamine and the dual action of resveratrol. By inhibiting the NLRP3 inflammasome, the scaffold shifts lipopolysaccharide-stimulated macrophages from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, as evidenced by reduced iNOS expression (from 19.62 to 3.43) and increased ARG-1 expression (from 2.06 to 6.04). Furthermore, the scaffold promotes the differentiation of injured PC12 cells into MAP2-positive neurons. In the PCP-Res-NGF (LPS-PR) group, the neurite length reached 119.59 μm, representing a 13.26% increase compared to the LPS-only control group. This scaffold provides a promising therapeutic platform for spinal cord injury repair through synergistic antioxidant, anti-inflammatory and neurodifferentiation-promoting effects.
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高影响因子
ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Xiaohong Yin,Yujuan Liu,Guancheng Zhan,Yichao Chen,Lixia Yu,Hongxia Wan,Xiaolin Chen,Peng Zhang,Huijun Zeng,Xiaodong Cao,Huichang Gao
The clinical translation of electroactive nerve conduits is often hindered by the trade-off between electrical performance and biodegradability, as well as the rapid clearance of neurotrophic factors which limits their ability to act in concert with long-term electrical stimulation. In this study, we engineered a fully biodegradable, self-powered multifunctional conduit by integrating piezoelectric poly(l-lactic acid) (PLLA) matrix with conductive reduced graphene oxide (rGO) within a flexible poly(l-lactide-co-ε-caprolactone) (PLCL) scaffold. This unique piezoelectric-conductive hybrid enabled efficient charge generation under mechanical stress and rapid signal transmission, creating an intrinsic electroactive microenvironment without external power sources. A polydopamine coating was further employed to enable sustained NGF release, extending the bioactive window of the scaffold. In vitro cell experiments demonstrated this dual-electroactive platform synergistically enhanced Schwann cells myelination, and promoted neuronal differentiation and neurite outgrowth in PC12 cells. Mechanistically, the in situ generated electrical activity amplified NGF-induced intracellular Ca2+ influx, leading to sustained mitochondrial activation and elevated ATP production, providing the bioenergetic foundation for enhanced regeneration. In a rat 10 mm sciatic nerve defect model, the conduit effectively accelerated functional recovery, reduced muscle atrophy, and promoted axonal regeneration and remyelination, achieving outcomes comparable to autografts. This work demonstrated that maintaining sustained copresence of self-generated electrical cues and neurotrophic support within a fully resorbable platform effectively enhances peripheral nerve regeneration.
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MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2026
·
IF 3.7
Bai Qiufang,Li Zhe,Chen Jing,Liu Man,Shao Xiaodan,Chen Xiaochi,Piao Fengyuan,Fang Linlin
N-hexane is a widely used aliphatic hydrocarbon solvent that can cause central–peripheral neuropathy. Compared to peripheral nerve tissue, spinal nerve tissue is more vulnerable and typically non-regenerable. However, no effective treatments are currently available. Stem cells are attractive therapeutic cells because of their extensive self-renewal and pluripotent differentiation abilities. Accordingly, numerous studies are focused on their restorative potential. In the present study, we investigated the effects and mechanisms of stem cell therapy on spinal nerves damaged by 2,5-HD (a proximate toxic metabolite of n-hexane). Our results showed that spinal axonopathy induced by 2,5-HD was alleviated by bone mesenchymal stem cell (BMSC) transplantation. Further, by examining the expression of molecules associated with axonal outgrowth, NGF signaling was found to be involved in the regeneration of spinal axons. Moreover, intervention experiments showed that PTEN was also an essential component of BMSC therapy. Conclusively, our data suggested that BMSC transplantation can alleviate spinal injury induced by 2,5-HD through AKT/mTOR/CREB by NGF-dependent and -independent pathways.
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高影响因子
ONCOGENE
·
2026
·
IF 9.1
Liu Pengpeng,Wang Huizhen,Yu Kexun,Ma Mengdi,Yang Xiongwei,Wang Yuexiang,Li Yongxiang
Lymphangiogenesis drives gastric cancer lymph node (GC LN) metastasis via neuro-immune-cancer interactions in the tumor microenvironment. However, the underlying mechanisms remain incompletely understood. Here, we demonstrate that chronic stress (CS) in GC patients correlates with poorer short-term prognosis, perineural/lymphovascular invasion, and advanced LN staging. Mechanistically, CS-induced neutrophil extracellular traps (NETs) are key mediators of LN metastasis. Inhibiting NETs suppressed popliteal LN metastasis and lymphangiogenesis. In vitro and in vivo experiments revealed that CS upregulated acetylcholine (ACh) and choline acetyltransferase (ChAT) levels, with ACh directly inducing NETs formation in a dose-dependently. Exogenous ACh increased LN metastasis (volume), whereas gastric vagotomy attenuated CS-mediated orthotopic tumor growth. Functional assays confirmed that ACh-driven NETs enhanced GC cell malignant behaviors, accelerated adhesive suspension state transformation via extracellular matrix remodeling, and activated a feedforward ACh-NGF axis. This triggered PKC-γ/STAT3-S100A8/A9-ROS cascade, mediating NETs formation and upregulating VEGFA/C. Protein analysis showed CD300ld overexpression in CS + GC tissues, independent of ACh signaling. Notably, combined targeting of the NGF/TrkA and CD300ld exerted synergistic anti-LN metastatic and lymphangiogenic effects. Collectively, this study elucidates a CS-driven mechanism regulating NETs to promote GC LN metastasis and identifies NGF/TrkA and CD300ld as therapeutic targets for GC LN metastasis.
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Theranostics
·
2020
·
IF 8.579
Teng Ma,Yafeng Yang,Xin Quan,Lei Lu,Bing Xia,Jianbo Gao,Fengyu Qi,Shengyou Li,Laihe Zhao,Liangwei Mei,Yi Zheng,Yanbing Shen,Zhuojing Luo,Yan Jin,Jinghui Huang
Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo . The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro , enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.
研究领域:
组织工程
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神经科学
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生物材料
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再生医学
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Regenerative Biomaterials
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2024
·
IF 5.6
Hong Juncong,Wu Dongze,Wang Haitao,Gong Zhe,Zhu Xinxin,Chen Fang,Wang Zihang,Zhang Mingchen,Wang Xiumei,Fang Xiangqian,Yang Shuhui,Zhu Jinjin
Peripheral nerve injury is a debilitating condition that have a profound impact on the overall quality of an individual’s life. The repair of peripheral nerve defects continues to present significant challenges in the field. Iron oxide magnetic nanoparticles (IONPs) have been recognized as potent nanotools for promoting the regeneration of peripheral nerves due to their capability as biological carriers and their ability to template the hydrogel structure under an external magnetic field. This research used a fibrin nanofiber hydrogel loaded with IONPs (IONPs/fibrin) to promote the regeneration of peripheral nerves in rats. In vitro examination of PC12 cells on various concentrations of IONPs/fibrin hydrogels revealed a remarkable increase in NGF and VEGF expression at 2% IONPs concentration. The biocompatibility and degradation of 2% IONPs/fibrin hydrogel were assessed using the in vivo imaging system (IVIS), demonstrating subcutaneous degradation within a week without immediate inflammation. Bridging a 10-mm sciatic nerve gap in Sprague-Dawley rats with 2% IONPs/fibrin hydrogel led to satisfactory morphological recovery of myelinated nerve fibers. And motor functional recovery in the 2% IONPs/fibrin group was comparable to autografts at 6, 9, and 12 weeks postoperatively. Hence, the composite fibrin hydrogel incorporating 2% IONPs exhibits potential for peripheral nerve regeneration.
研究领域:
神经科学
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生物材料
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组织工程
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再生医学
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Qianyi Zhang,Hongjun Zhuang,Xiaofei Wen,Yonghui Su,Jiamian Wang,Hao Qin,Jiaqian Wang,Zhaoshui Shangguan,Yiqun Ma,Jian Dong,Bo Tian,Xilei Li
Cancer neuroscience has revealed the pivotal role of neural pathways in tumor progression and cancer-associated pain, particularly in bone metastases. To address both tumor growth and pain, we developed a novel nanomedicine strategy that targets mitochondrial dysfunction in cancer cells. The engineered H-MnCa/3MA-ALD nanoparticle system combines hollow mesoporous manganese-calcium (H-MnCa) nanoparticles functionalized with alendronate (ALD) for bone targeting, and loaded with 3-Methyladenine (3MA) to inhibit autophagy. This system disrupts mitochondrial ATP production, exploiting the inherent vulnerability of mitochondria to oxidative stress, and enhances reactive oxygen species (ROS) generation. The elevated ROS selectively induces cancer cell death while also reducing the secretion of nerve growth factor (NGF). This dual-action mechanism not only inhibits tumor growth and metastasis but also alleviates cancer-induced bone pain by downregulating neuro-pain mediators such as p-STAT-3 and NGF. This approach overcomes traditional chemodynamic therapy (CDT) limitations, ensuring targeted mitochondrial damage and apoptosis while preventing protective mitophagy. In vivo studies further confirm that H-MnCa/3MA-ALD provides effective tumor eradication and pain relief, offering a comprehensive solution for both cancer progression and pain management.
研究领域:
癌症研究
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神经科学
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纳米技术
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分子生物学
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Science China-Life Sciences
·
2014
·Vol. 57
·期 2
·256-262
·
IF 1.512
Zhang LuZhong,Zhou YouLang,Li GuiCai,Zhao YaHong,Gu XiaoSong,Yang YuMin
Peripheral nerve functional recovery after nerve injury generally requires multiple growth factors by synergistic effect. However, the optical combination of multiple synergistic growth factors for axonal regeneration has been scarcely considered up to now. Meanwhile, the use of growth factors in promoting nerve regeneration was limited by its short biological half-life in vivo , its vulnerability to structure disruption or hydrolyzation, leading to loss of bioactivity. Herein, a novel polymeric nanoparticle delivery system composed of heparin and ɛ -poly-L-lysine (PL) was prepared for control release of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF). The nanoparticles were synthesized by polyelectrolyte complexation in aqueous solution at room temperature, followed by cross-linking with biological genipin. The obtained nanoparticles had a spherical shape, with a mean diameter of about 246 nm, and high growth factors encapsulation efficiency as well as good stability. NGF and bFGF were encapsulated in the nanoparticles and showed a continuous and slow release behavior in vitro . The bioactivities of the released growth factors were evaluated, and exhibited the synergistic effect. The controlled release of the dual synergistic growth factors would improve the treatment of peripheral nerve injury to mimic the natural cellular microenvironments.
研究领域:
生物医学工程
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神经科学
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材料科学
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药学
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Pharmaceuticals
·
2024
·Vol. 17
·期 9
·1181
·
IF 4.3
Zeting Huang,Lanyue Zhang,Jie Xuan,Tiantian Zhao,Weihua Peng
Atopic dermatitis (AD) is a persistent and recurrent inflammatory skin condition with a genetic basis. However, the fundamental reasons and mechanisms behind this phenomenon remain incompletely understood. While tea extracts are known to reduce histamine-induced skin allergies and inflammation, the specific mechanisms by which various types of Chinese tea provide their protective effects are still not fully elucidated. In this study, a model of skin itching induced by histamine is used to explore the functions and mechanisms of three types of tea extract (Keemun black tea (HC), Hangzhou green tea (LC), and Fujian white tea (BC)) in alleviating histamine-induced dermatitis. The components of three tea extracts are identified by UPLC-Q-TOF-MS, and we found that their main components are alkaloids, fatty acyls, flavonoids, organic acids, and phenols. The inhibitory effects of three types of tea extract onEscherichia coli(E. coli) andStaphylococcus aureus(S. aureus) in skin injury are investigated by MIC and flow cytometry. The three types of tea extract have an inhibitory effect on the growth of bacterial flora, with HC showing the best inhibitory activity. The effect of the three types of tea extract on histamine-induced dermatitis is also evaluated. Furthermore, itchy skin experiments, HE staining, toluidine blue staining, and immunohistochemical staining of mouse skin tissues were performed to determine the variations of scratching, epidermal thickness, mast cell number, IL-1β, and NGF content after the administration of the tea extracts. The three types of tea extracts all alleviate and inhibit skin itching, epidermal hyperplasia, and allergic dermatitis. BC effectively alleviates epidermal hyperplasia caused by skin allergies, and LC significantly downregulates NGF. HC reduces histamine-induced mast cell infiltration and downregulates IL-1β to alleviate skin itching. Consequently, tea emerges a potent natural product that can inhibit the growth of skin wound bacterial flora and exhibit skin repair effects on histamine-induced allergic dermatitis.
研究领域:
药理学
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皮肤病学
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茶科学
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免疫学
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BRAIN RESEARCH BULLETIN
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2024
·
IF 3.5
Yingying Sun,Dandan Zhou,Anlan Liu,Yu Zhou,Yang Zhao,Yuan Yuan,Weifeng Guo,Jianxiang Li
Liangxue Tongyu Prescription (LTP) is a classic herbal formula for treating acute intracerebral hemorrhage (AICH) in China. Previous studies have shown that LTP significantly ameliorates neurological impairments and gastrointestinal dysfunction in patients with AICH. However, the underlying molecular mechanism remains unclear. The aim of this study is to investigate whether LTP exerts its neuroprotective effect on AICH rats through the microbiota-gut-brain axis and explore its potential underlying mechanism. In the current study, AICH models were established by injecting autologous whole blood into the right caudate nucleus of rats. Behavioural and pathological evaluations demonstrated that LTP ameliorated neuronal and intestinal damage in AICH rats. Analysis via western blot, quantitative real-time PCR, immunohistochemistry (IHC) and tunel staining indicated that LTP upregulated the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor(NGF) and reduced neuronal cell apoptosis. Additionally, 16S rDNA sequencing revealed that LTP mitigated dysbiosis of intestinal microbiota in AICH rats. LTP increased the levels of noradrenaline (NA), dopamine (DA), glutamate (GLU) and modulated brain-gut peptides such as gastrin (GAS), motilin (MTL), ghrelin in AICH rats. Furthermore, LTP enhanced vagus nerve discharge. In summary, this research provides evidence suggesting that LTP’s influence on AICH may involve modulation of the microbiota-gut-brain axis, offering a potential scientific rationale for its therapeutic efficacy in improving outcomes of AICH.
研究领域:
神经科学
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药理学
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微生物学
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分子生物学
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COMPOSITES PART B-ENGINEERING
·
2024
·
IF 12.7
Fangyu Qiao,Yang Zou,Yonggang Lv
Peripheral nerves and blood vessels regulate the development process of bone tissue by delivering neural and vascular-related cytokines. However, challenge of preventing the loss of neural and vascular growth factors and ensuring their long-term availability for bone defects was often been overlooked. The current study designed a hybrid cell membrane with specific surface receptors for calcitonin receptor (CTR) and vascular endothelial growth factor receptor (VEGFR) through overexpressed the CTR receptor gene ( Calcr ) and the VEGFR 1 gene ( Flt-1 ). The bone repair matrix functionalized by the hybrid cell membrane (GCMs) had collecting property for neurogenic growth factor (NGF) and vascular endothelial growth factor (VEGF). Furthermore, GCMs enhanced neural and vascular differentiation in mesenchymal stem cells (MSCs) and stimulated osteogenic differentiation of MSCs through neural and vascular-related paracrine signals. GCMs also facilitated the angiogenesis and neurogenesis around bone defects, further promoted the repair of rat skull defects. This study suggests a promising approach for using cell membranes to harvest growth factors for innervation and vascularization in bone reconstruction.
研究领域:
组织工程
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再生医学
·
骨生物学
·
干细胞研究
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Biomaterials Advances
·
2022
·
IF 0
Xiaoyan Wang,Weijia Zheng,Zhenzu Bai,Shan Huang,Kai Jiang,Haoming Liu,Long Liu
There is a significant clinical demand for bone repair materials with high efficacy. This study was designed to fabricate nanofibrous scaffolds to promote bone defect regeneration using magnesium doped mesoporous bioactive glass (MBG), a fusion protein Osteocalcin-Osteopontin-Biglycan (OOB), silk fibroin (SF) and nerve growth factor (NGF) for facilitating accelerated bone formation. We found that MBG adsorbed with OOB ( [email protected] ) as core, and SF adsorbed with NGF ( [email protected] ) as shell to fabricate the nanofibrous scaffolds ( [email protected] / [email protected] ) through coaxial electrospinning. [email protected] / [email protected] scaffolds could effectively mimic the component and structure of bone matrix. Interestingly, we observed that [email protected] / [email protected] scaffolds could substantially promote bone mesenchymal stem cells (BMSCs) osteogenesis through stimulating Erk1/2 activated Runx2 and mTOR pathway, and it could also activate the expression level of various osteogenic marker genes. Intriguingly, [email protected] / [email protected] scaffolds could also enhance BMSCs induced neural differentiation cells differentiated into neuron, and activate the expression of the different neuron specific marker genes. Moreover, it was found that [email protected] / [email protected] scaffolds accelerated bone regeneration with neurogenesis, and new neurons were formed in Haversian canal in vivo . Consistent with these observations, we found that Erk1/2 and mTOR signaling pathways also regulated osteogenesis with the neurogenesis process from RNA sequencing result. Overall, our findings provided novel evidence suggesting that [email protected] / [email protected] scaffolds could function as a potential biomaterial in accelerating bone defect regeneration with neurogenesis, as well as in recovering the motor ability and improving the quality of life of patients.
研究领域:
材料科学
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组织工程
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生物医学工程
·
再生医学
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